4V30: Cereblon Isoform 4 From Magnetospirillum Gryphiswaldense In Complex With Lenalidomide

Citation:
Abstract
Thalidomide and its derivatives lenalidomide and pomalidomide are important anticancer agents but can cause severe birth defects via an interaction with the protein cereblon. The ligand-binding domain of cereblon is found, with a high degree of conservation, in both bacteria and eukaryotes. Using a bacterial model system, we reveal the structural determinants of cereblon substrate recognition, based on a series of high-resolution crystal structures. For the first time, we identify a cellular ligand that is universally present: we show that thalidomide and its derivatives mimic and compete for the binding of uridine, and validate these findings in vivo. The nature of the binding pocket, an aromatic cage of three tryptophan residues, further suggests a role in the recognition of cationic ligands. Our results allow for general evaluation of pharmaceuticals for potential cereblon-dependent teratogenicity.
PDB ID: 4V30Download
MMDB ID: 125694
PDB Deposition Date: 2014/10/15
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 1.85  Å
Source Organism:
Similar Structures:
Biological Unit for 4V30: monomeric; determined by author and by software (PISA)
Molecular Components in 4V30
Label Count Molecule
Protein (1 molecule)
1
Cereblon Isoform 4
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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